Delmas was considered by some to be a top-10 prospect at his position in the 2009 NFL Draft.[4] Prior to the draft, ESPN's Todd McShay said Delmas had a chance to get drafted in the first three rounds.[5] Delmas was drafted 1st in the second round by the Detroit Lions (33rd overall). Delmas was named 2009 Detroit Lions Rookie of the Year in voting by the Detroit Sports Broadcasters Association.

Delmas was signed by the Lions to a four-year contract. Delmas returned a 65-yard fumble for a touchdown in Week 1 of the 2009 season against the New Orleans Saints. Delmas won September's rookie defensive player of the month award.[7] On December 20, 2009, Delmas became the first rookie in NFL history to record an interception return for a touchdown, a fumble return for a touchdown and a safety in the same season.[8] He is only the second player in NFL history to accomplish the feats in the same season.

Delmas was named a Pro Bowl alternate for the NFC after the 2010 NFL season.[9]

Delmas was named a Pro Bowl alternate for the NFC after the 2011 NFL season, despite missing five games to injuries.[10]

On March 15, 2013, Delmas re-signed with the Lions to a two-year contract worth $9.465 million.[11]

On Sunday October 6, 2013, Lion's Center Dominic Raiola was involved in an incident of trash-talking and hate-speech to members of the UW-Madison marching band. Louis Delmas is credited with both apologizing for his teammate's actions and having a word with Raiola off the field.[12]

On March 10, 2014, Delmas signed a one-year deal with the Miami Dolphins. The contract is worth a maximum of $3.5 million.[13] On December 8, 2014 he was placed on Injured reserve after he tore his right ACL against the Baltimore Ravens.[14]